JournalofMedicineandLifeVol.4,Issue4,OctoberDecember2011,pp.

387394

Probiotics and periodontal health

Gupta G.
Department of Periodontics, Institute of Dental Studies and Technologies, Modinagar, UP, India

Correspondence to: Gupta Geeti, Senior Lecturer,
Institute of Dental Studies and Technologies, National Highway- 58,
Near Kadrabad police check pos, Modinagar, Uttar Pradesh, India 201201
Phone (mobile): 9412101475; E-mail: drgeeti_gupta@yahoo.com

Received: April 14th, 2011 Accepted: September 24th, 2011


Abstract
Periodontitis is one of the most common chronic inflammatory diseases. The etiology is clearly bacterial and a number of putative
bacterial pathogens have been associated with the disease, including Aggregatibacter actinomycetemcomitans, Tannerella forsythus
and Porphyromonas gingivalis. Comparatively, little attention has been paid to the identification of health-associated and potentially
beneficial bacterial species that may reside in the gingival sulcus. Probiotic technology represents a breakthrough approach to
maintaining oral health by using natural beneficial bacteria, commonly found in healthy mouths, to provide a natural defense against
those bacteria which are thought to be harmful to teeth and gums. This article endeavors to introduce the concepts of probiotics in
periodontics.

Key Words: Probiotics; Synbiotics; Periodontitis;

Bacterial replacement therapy; Halitosis

Introduction
Periodontitis is a multifactorial disease that
encompasses the hard and soft tissue, microbial
colonization (with or without invasion), inflammatory
responses and adaptive immune responses. The
complexity of the local tissue components, including
bacteria and/or their products and virtually all aspects of
host response mechanisms, has complicated our ability to
elucidate the critical protective functions in the tissues and
has continually provided evidence for the potential of host
destructive factors as the ultimate causative parameters
in the disease. [1] Conventional treatment modalities of
periodontal disease include non-surgical and surgical
management, which emphasizes mainly on mechanical
debridement, often accompanied by antibiotics. These
treatment modalities are aimed at eliminating the entire
microflora irrespective of their pathogenicity. Due to the
emergence of antibiotic resistance and frequent
recolonization of treated sites with pathogenic bacteria,
there was need for a new treatment paradigm to be
introduced to periodontal disease. The need was fulfilled
by introduction of Probiotics and bacterial replacement
therapy in the field of periodontics.
Probiotics and prebiotics
Probiotics are defined as living microorganisms,
principally bacteria, that are safe for human consumption
and, when ingested in sufficient quantities, have beneficial
effects on human health, beyond basic nutrition. This
definition has been approved by the United Nations Food
and Agriculture Organization (FAO) and the World Health
Organization (WHO). [2]
Prebiotics (i.e. inulin-type fructans, maltodextrin,
fructooligosaccharides and galactooligosaccharides) have
been defined as non-digestible oligosaccharides that
affect the proliferation of resident commensal bacteria that
may then exert probiotic effects. [3] More recently, the
definition has been refined to include selectively
fermented ingredients that allow specific changes in the
composition and/or activity of the resident microflora that
confer benefits upon host well-being and health. [4]
Prebiotics and probiotics often work in synergy
and, when combined in the same product, are known as
synbiotics. It appears that synbiotics increase survival of
probiotic bacteria, stimulating their growth in the intestinal
tract and improving the balance of health-promoting
bacteria. [5]
History
The dietary use of living microorganisms has a
long history. Mention of cultured dairy products is found in
the bible and the sacred books of Hinduism. Sacred milks
and cultured dairy products such as kefir, koumiss, liben

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 JournalofMedicineandLifeVol.4,Issue4,OctoberDecember2011
and dahi, were often used therapeutically before the
existence of microorganisms was recognized. [6]
Probiotics have been used for decades in
fermented products, but potential use of probiotics as a
nutritional medical therapy has not been formally
acknowledged. [7] Metchnikoff was the first to state that
probiotics could provide a health benefit, and proposed
that Bulgarian people had a longer longevity due to
fermented milk containing viable bacteria. Probiotic
term, as opposed to antibiotic, was initially proposed by
Lilley and Stillwell in 1965. First probiotic species to be in-
troduced in research was Lactobacillus acidophilus by
Hull et al. in 1984; followed by Bifidobacterium bifidum by
Holcombh et al. in 1991.
In 1994, the World Health Organization
deemed probiotics to be the next-most important immune
defense system when commonly prescribed antibiotics
are rendered useless by antibiotic resistance. These
incidences paved way for a new concept of probiotics in
medicine and dentistry. [8-10]
Mechanisms of action
Probiotics
The mechanism of action vary according to the
specific strain or combinations of strains used, the
presence of prebiotics and the condition that is being
treated, as well as the stage of the disease process in
which the probiotic is administered. [11] There are
common themes emerging in studies of the modes of
action of probiotics and numerous mechanisms have
been proposed [11,12] including:
Inhibition of pathogen adhesion, colonization and
biofilm formation
Induction of expression of cytoprotective proteins
on host cell surfaces
Inhibition of collagenases and reduction of
inflammation associated molecules
Stimulation and modulation of the host immune
system, e.g. by reducing production of pro-
inflammatory cytokines through actions on NFB
pathways, increasing production of anti-
inflammatory cytokines such as IL-10
Modulation of cell proliferation and apoptosis eg.
Prevention of cytokine induced apotosis
Killing or inhibition of growth of pathogens
through production of bacteriocins or other
products, such as acid or peroxide, which are
antagonistic towards pathogenic bacteria.
Probiotics can also modify the surrounding
environment by modulating the pH and/or the
oxidationreduction potential, which may
compromise the ability of pathogens to become
established.
Prebiotics
The major mechanism of action of prebiotics is
assumed to be indirect, i.e. facilitating the proliferation of
beneficial components of the resident microflora. Some
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prebiotics also exert direct effects on the host;
independent of their effects on resident bacterial
populations. [13] These include stimulation of expression
of IL-10 and interferon , enhancement of IgA secretion,
modulation of inflammatory responses to pathogens and
stabilization of the gut mucosal barrier. Additionally,
prebiotics with enhanced function have been designed.
These oligosaccharide derivatives contain sugars that are
specific epithelial cell receptors to which pathogens
adhere and they, therefore, provide decoy adhesion
sites and cause pathogens to adhere to luminal contents
rather than to epithelial cells. [14]
Oral microbiota in health and disease
More than 700 species have been detected in
the human mouth and the resident microbiota of an
individual may comprise 30 to >100 species.15 A wide
variety of sites in the mouth are heavily colonized.
Supragingival and subgingival plaque form through
sequential and specific adhesive interactions that result in
a complex climax community. [16] The tongue is heavily
colonized and micro-organisms on the dorsum of the
tongue are reservoirs for supragingival and subgingival
plaque and salivary microbial populations. [17] Many oral
bacteria, especially streptococci, also survive within
buccal epithelial cells. [18]
Functions of the resident microbiota
Resident microbiota does not play merely a
passive role, but actively contributes to the maintenance
of health. The large, diverse resident microbial
communities that colonize mucosal sites co-exist with a
host, producing harmful effects only if the host becomes
immunocompromised, if the resident microbial
populations are suppressed or if micro-organisms reach
sites to which they do not normally have access (i.e.
through trauma). Resident microbial populations
contribute to host protection through development of the
immune system, [19] the maintenance of healthy oral
tissue by influencing expression of mediators such as
intracellular adhesion molecule 1 (ICAM-1), E-selectin
and IL-8, [20] modulating immune responses and
enhancing cellular homeostatic mechanisms. [21]
Defining the resident microbiota
Resident oral microbial populations are site-
specific as well as highly diverse. Kilian et al. [22] list the
following species as true oral commensal
microorganisms: Streptococcus mitis, Streptococcus
oralis, Actinomyces naeslundii, Fusobacterium nucleatum,
Haemophilus parainfluenzae, Eikenella corrodens and
some species of Prevotella.
Microbial populations associated with oral disease
The most common oral diseases are caries and
periodontitis, which result from a shift in the balance of the
resident microbiota at a site. In caries, there are increases
 JournalofMedicineandLifeVol.4,Issue4,OctoberDecember2011
in acidogenic and acid-tolerating species such as mutans
streptococci and lactobacilli, although other bacteria with
similar properties can also be found and bifidobacteria,
non-mutans streptococci, Actinomyces spp.,
Propionibacterium spp., Veillonella spp. and Atopobium
spp. have also been implicated as significant in the
etiology of this disease. [23]
In periodontal diseases, there is an increase in
plaque mass and a shift towards obligatory anaerobic and
proteolytic bacteria, many of which are Gram negative
and currently unculturable. The host damage that occurs
during periodontal disease arises through the combined
activities of subgingival biofilms and the host responses to
these diverse bacterial populations. [16]
Candida albicans and other Candida species are
present in low levels in oral microbial communities and
can cause oral candidiasis and denture- associated
stomatitis. [24] Halitosis is most often the result of
production of malodorous metabolic endproducts
(especially volatile sulphur compounds) by oral bacteria,
in particular Gram negative anaerobes. [25]
Probiotics of interest
The most common probiotic strains belong to the
genera Lactobacillus and Bifidobacterium. Lactobacillus
species from which probiotic strains have been isolated
include L. acidophilus, L. johnsonii, L. casei, L.
rhamnosus, L. gasseri, and L. reuteri. Similarly, the
bifidobacterium strains include B. bifidum, B. longum, and
B. infantis. Lactobacilli can produce different antimicrobial
components including organic acids, hydrogen peroxide,
low-molecular weight antimicrobial substances,
bacteriocins and adhesion inhibitors and thus have gained
prominence as probiotics. Streptococcus Oralis and
Streptococcus Uberis have been shown to inhibit the
growth of pathogens both in the laboratory and animal
models. [26]
Probiotics in prevention of periodontal diseases
Periodontal disease is classified into 2 types:
gingivitis and periodontitis. Gingivitis is characterized by
inflammation limited to the gingiva, whereas periodontitis
is a progressive, destructive disease that affects all
supporting tissues of the teeth, including the alveolar
bone. [27] The main pathogenic agents associated with
periodontitis are P. gingivalis, Treponema denticola,
Tannerella forsythus and Aggregatibacter
actinomycetemcomitans. [27] These bacteria have a
variety of virulent characteristics allowing them to colonize
the subgingival sites, escape the hosts defense system
and cause tissue damage. [27] The persistence of the
hosts immune response also constitutes a determining
factor in progression of the disease. [27]
There are fewer experimental studies exploring
probiotic use in periodontal diseases, partly reflecting a
poorer understanding of the precise etiology of the
disease and of the conditions that promote health.
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Grudianov et al [28] studied the effect of probiotic tablets on
gingivitis and different grades of periodontitis and observed that
probiotic treatment resulted in better microbiota normalization
than control group. In one recent study, the prevalence of
lactobacilli, particularly L. gasseri and L. fermentum, in the
oral cavity was greater among healthy participants than
among patients with chronic periodontitis. [29] Various
studies have reported the capacity of lactobacilli to inhibit
the growth of periodontopathogens, including P.
gingivalis, Prevotella intermedia and A.
actinomycetemcomitans. [29] Together, these
observations suggest that lactobacilli residing in the oral
cavity could play a role in the oral ecological balance.
In a study by Krasse et al, [30] patients with
moderate to severe gingivitis who were given either one
of two L. reuteri formulations had reduced plaque and
gingivitis scores compared to a placebo group. Although
the exact mechanisms of action of L. reuteri remain to be
elucidated, previous studies have suggested at least 3
plausible possibilities: first, L. reuteri is known for its
secretion of 2 bacteriocins, reuterin and reutericyclin, that
inhibit the growth of a wide variety of pathogens; [31]
second, L. reuteri has a strong capacity to adhere to host
tissues, thereby competing with pathogenic bacteria; [32]
and third, the recognized anti-inflammatory effects of L.
reuteri on the intestinal mucosa, leading to inhibition of
secretion of proinflammatory cytokines, could be the
foundation for a direct or indirect beneficial effect of this
bacterium on people with periodontal disease. Vivekanda
et al [33] also confirmed the plaque inhibitory, anti-
inflammatory and antimicrobial effects of L. reuteri
Prodentis.
Riccia and colleagues [34] recently studied the
anti-inflammatory effects of Lactobacillus brevis in a group
of patients with chronic periodontitis. A significant
reduction in salivary levels of prostaglandin E2 (PGE2)
and matrix metalloproteinases (MMPs) was observed.
The authors suggested that the beneficial anti-
inflammatory effects of L. brevis could be attributed to its
capacity to prevent the production of nitric oxide and,
consequently, the release of PGE2 and the activation of
MMPs induced by the nitric oxide. [34] However, L. brevis
may also be antagonistic, leading to a reduction in the
quantity of plaque and therefore an improvement in the
gingival index.
Shimauchi et al [35] reported that the regular
(three times daily for eight weeks) intake of tablets
containing Lactobacillus salivarius resulted in benefits in
terms of pocket probing depth and plaque index in
individuals at high risk of periodontal disease (smokers)
compared to a placebo control group. [35] Other studies
have aimed to identify organisms that have the potential
for probiotic action that may protect against periodontal
diseases. Some oral strains of lactobacilli and
streptococci [36] and bifidobacteria [37] have been
reported to have in vitro inhibitory activity against
periodontal pathogens, while others are more active
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 JournalofMedicineandLifeVol.4,Issue4,OctoberDecember2011
against mutans streptococci. [36] Koll-Klais et al [38]
observed that Lactobacillus gasseri strains isolated from
periodontally healthy subjects were more efficient at
inhibiting the growth of A. actinomycetemcomitans than
strains from periodontally diseased subjects. L. gasseri
also inhibited the growth of P. gingivalis and P.
intermedia; this correlated with an inverse relationship
between carriage of homofermentative lactobacilli and
subgingival colonization by A. actinomycetemcomitans, P.
gingivalis and P. intermedia. Ishikawa et al. [39] observed
in vitro inhibition of P. gingivalis, P. intermedia and
Prevotella nigrescens by L. salivarius. Daily ingestion of L.
salivarius-containing tablets resulted in reduced salivary
counts of these black pigmented anaerobes. The
mechanisms of inhibition of periodontal pathogens have
not been fully clarified. The inhibitory activity displayed by
homofermentative lactobacilli against periodontal
pathogens was principally related to their production of
acid, not to H2O2 or bacteriocin production. [38] Hojo et al
[37] suggested that bifidobacteria inhibit some black
pigmented anaerobes by competing for an essential
growth factor, vitamin K, although there was no significant
relationship between higher bifidobacterial counts and
lower black-pigmented anaerobe counts. Recently, a
bacteriocin purified from Lactobacillus casei killed P.
gingivalis but its use was proposed as a novel
chemotherapeutic agent rather than as strain
development for probiotic applications. [40] During the
fermentation process in milk, Lactobacillus helveticus
produces short peptides that act on osteoblasts and
increase their activity in bone formation. [41] These
bioactive peptides could thereby contribute to reducing
the bone resorption associated with periodontitis.
Recently Shimazaki and colleagues [42] used
epidemiological data to assess the relationship between
periodontal health and the consumption of dairy products
such as cheese, milk and yoghurt. The authors found that
individuals, particularly nonsmokers, who regularly
consumed yoghurt or beverages containing lactic acid
exhibited lower probing depths and less loss of clinical
attachment than individuals who consumed few of these
dairy products. A similar effect was not observed with milk
or cheese. By controlling the growth of the pathogens
responsible for periodontitis, the lactic acid bacteria
present in yoghurt would be in part responsible for the
beneficial effects observed.
Sunstar (Etoy, Switzerland) recently began
marketing the first probiotic specifically formulated to fight
periodontal disease. Gum Perio Balance contains a
patented combination of 2 strains of L. reuteri specially
selected for their synergetic properties in fighting
cariogenic bacteria and periodontopathogens. Each dose
of lozenge contains at least 2 108 living cells of L. reuteri
Prodentis. Users are advised to use a lozenge every day,
either after a meal or in the evening after brushing their
teeth, to allow the probiotics to spread throughout the oral
cavity and attach to the various dental surfaces.
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Guided periodontal pocket recolonization (Bacterial
replacement therapy) in Periodontics
Replacement therapy is also known as
probiotic therapy. The concept of bacterial replacement
therapy in periodontics was first introduced by Teughels
et al in 2007. They reported that the subgingival
application of a bacterial mixture including Streptococcus
sanguis, S. salivarius, and Streptococcus mitis after
scaling and root planing significantly suppressed the re-
colonization of Porphyromonas gulae (canine P.
gingivalis) and P. intermedia in a beagle dog model. [43]
Nackaerts et al [44] observed that the subgingival
application of beneficial oral bacteria (i.e. Streptococcus
sanguinis, Streptococcus salivarius and S. mitis) delays
recolonization by periodontal pathogens, reduce
inflammation, and improve bone density and bone levels
in a beagle dog model. This guided pocket recolonization
approach may provide a valuable addition or alternative to
the armamentarium of treatment options for periodontitis.
Probiotics in prevention of halitosis
Halitosis has many causes (including
consumption of particular foods, metabolic disorders,
respiratory tract infections), but in most cases it is
associated with an imbalance of the commensal
microflora of the oral cavity. [45] More specifically,
halitosis results from the action of anaerobic bacteria that
degrade salivary and food proteins to generate amino
acids, which are in turn transformed into volatile sulphur
compounds, including hydrogen sulphide and methyl
mercaptan and dimethyl sulphide. [45]
There have also been clinical and laboratory
studies of probiotics in their potential for preventing
halitosis. Peroxide production by strains of Weissella
cibaria (commonly present in fermented foods) isolated
from the mouths of healthy children, inhibited production
of volatile sulphur compounds that contribute to oral
malodour by F. nucleatum in vitro and in exhalations
following mouth-rinsing by adult volunteers with a
suspension of W. cibaria. [46] The success of W. cibaria
in reducing malodour may have also been because it
coaggregated efficiently with F. nucleatum [46] and
therefore competed with other late/secondary colonizers
for adhesion sites. Thus, W. cibaria may have probiotic
activities with potential for prevention of periodontal
disease. Volatile sulphur compounds, such as H2S and
mercaptoethanol, are produced by a range of periodontal
anaerobes. [47] The inhibition of these micro-organisms
by peroxide from W. cibaria may help reduce subgingival
plaque pathogenicity while its competition for
coaggregation sites may reduce the reservoir of micro-
organisms available for transmission into plaque.
One recent study [48] showed that certain
bacterial species, including Atopobium parvulum,
Eubacterium sulci and Solobacterium moorei,
predominate on the dorsal surface of the tongue among
people with halitosis. Conversely, another species,
 JournalofMedicineandLifeVol.4,Issue4,OctoberDecember2011
Streptococcus salivarius, was detected most frequently
among people without halitosis and is therefore
considered a commensal probiotic of the oral cavity. S.
salivarius is known to produce bacteriocins, which could
contribute to reducing the number of bacteria that produce
volatile sulphur compounds. [49]
S. salivarius K12 produces salivaricin, a
lantibiotic with inhibitory activity towards most
Streptococcus pyogenes. [50] This strain has been
commercially promoted as a probiotic that is reported to
be protective against throat infections and oral malodour.
[50] The importance of strain selection for probiotic use is
illustrated by the fact that some S. salivarius strains differ
from K12 in some important activities; one strain
increased production of malodorous products by
facilitating P. gingivalis metabolism of salivary mucins [51]
and another up-regulated IL-8 secretion by oral epithelial
cells [52] in contrast to the down-regulation observed in
response to K12.
Residence time of probiotics in oral cavity
Residence time of probiotics in oral cavity after treat-
ment withdrawal was studied by aglar et al. [53] A reduced S.
mutans level was shown after a two-week use of a L. reuteri-
enriched yoghurt; effects were observed during use and for a
few days after discontinuation. A loss of L. reuteri colonization
was observed by Wolf et al. [54] two months after having
discontinued probiotic use. L. rhamnosus GG administration
and oral cavity colonization was studied by Yli-Knuuttila et al
[55]; the authors concluded that permanent colonization in oral
cavity was unlikely (although possible in some cases) and
suggested the probiotic to be used on a regular basis. Binding
strength of 17 Lactobacillus strains and 7 bifidobacteria strains
to saliva and oral mucous membrane was variable in different
strains, according to a study by Haukioja et al. [56] Such a
strength variation caused an increased residence time of
probiotic in oral cavity. Latency time of probiotic S. salivarius
K12, 4 tablets/day for 3 days, was assessed in several oral
cavity areas in a 35-day follow-up, by Horz et al. [57] Probiotic
could be found on oral mucous membrane, tongue and in
stimulated saliva for more than 3 weeks, with a gradually
reduced S. salivarius K12 level being detected beginning 8
days after treatment withdrawal.
Potential risks of probiotic therapy
Different strains of a species may not all
possess characteristics that enable them to be probiotics
and rigorous strain selection for the disease concerned is
complex but essential. [58] Some probiotic strains have
been in use for many years and have excellent safety
records. [59] Most probiotic bacteria are weakly
proteolytic and, for example, Lactobacillus bulgaricus,
was shown to be incapable of degrading some host tissue
components. [60] However, there have been some cases
of bacteraemia and fungaemia associated with probiotic
use, although these have been in subjects who are
immunocompromised, [61] or who suffer from chronic
disease [59] or short gut syndrome. [62] Other
predisposing factors include prior prolonged
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hospitalization and prior surgical intervention. [61] An
individual who had been taking L. rhamnosus in a
probiotic preparation developed Lactobacillus endocarditis
following dental treatment. [63] In Finland, however, there
has not been an increase in bacteremia associated with
probiotic lactobacilli following the increase in the use of
these products since 1990. [64] The species that most
commonly exhibit probiotic benefits are lactobacilli and
other lactic acid bacteria, and the production of acid is
often thought to be an important component of their
protection against pathogenic colonization. However,
Lactobacillus spp. and acid production by acidogenic
plaque populations play a significant part in the
development of caries, and a probiotic strain of L.
salivarius has been shown to be cariogenic in a rat model.
[65] A number of probiotic lactobacilli and bifidobacteria
produce acid from fermentation of dietary sugars in vitro.
[66] There are conflicting data on the salivary lactobacilli
levels following probiotic usage. Some studies have
reported no effects, [67] others have found trends for an
increase, [68] while others have detected statistically
significant rises in counts of salivary lactobacilli. [69]
There is a converse risk in that the control or prevention
of caries may indirectly affect periodontal pathogens. It
has been known for many years that streptococci, through
production of hydrogen peroxide, inhibit the growth of
putative periodontal pathogens, leading to early proposals
that interactions between groups of micro-organisms
within plaque can influence the development of disease or
actively contribute to the maintenance of health, [70] and
lactobacilli and bifidobacteria also inhibit the growth of a
range of periodontal pathogens. [70] It is clear that careful
selection of the strain to be ingested for a particular
disease is essential and the mode and timing of
administration can be crucial, as well as the age and
health of the individual taking the probiotic. There is a
sufficient knowledge base for major and minor risk factors
to have been proposed for administration of probiotics to
prevent intestinal conditions, [59] but this knowledge base
for oral applications is clearly more distant. One of the
biggest problems to overcome may be that the probiotic
activities and micro-organisms that protect against oral
disease could increase the risk of development of dental
caries. Therefore, a prebiotic-type approach to enhance
endogenous beneficial commensals may be more
attractive. It will also be a challenge to ensure that modes
of delivery are developed that provide sufficient retention
and exposure times in the mouth that will allow probiotics
to colonies plaque or prebiotics to enter into plaque or
mucosal biofilms and influence microbial metabolism
within them.
Conclusion
Probiotics are emerging as a fascinating field in
oral medicine. This concept prompts a new horizon on the
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 JournalofMedicineandLifeVol.4,Issue4,OctoberDecember2011

relationship between diet and oral health. The use of
probiotics for use in oral care applications is gaining
momentum. There is increasing evidence that the use of
existing probiotic strains can deliver oral health benefits.
Further work will be needed to fully optimize and quantify
the extent of this benefit. In parallel, the potential of
prebiotics to maintain and enhance the benefits provided
by the resident oral microbiota will be investigated.
However, whether considering probiotics or prebiotics, it
will be essential to develop an understanding of the broad
ecological changes induced in the mouth by their
ingestion and the long-term consequences of their use on
oral health and disease. Further studies to understand the
References
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of probiotics. Hence, systematic studies and randomized
controlled trials are needed to find out the best probiotic
strains and means of their administration in different oral
health conditions. Finally, possibilities to genetically
modify or engineer potential probiotic strains may offer all
new visions. Better scientific understanding and extended
research of these tiny forms of life and their effect on
humans in the treatment of periodontal diseases might
further broaden the field of potential applications.

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